A Phase 1, Single- and Multi-Dose, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-TTRSC (Revusiran) in Healthy Volunteers

NCT01814839 | Completed Phase 1

• 1 other identifier: ALN-TTRSC-001
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-TTRSC (revusiran) in healthy volunteer subjects.

Conditions

TTR-mediated Amyloidosis

Keywords

RNAi therapeutic

Outcome Measures

Primary Outcomes (1)

• The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study drug discontinuation.

  Up to 63 days

Secondary Outcomes (4)

• Pharmacokinetics (PK) of ALN-TTRSC (revusiran) (Cmax, tmax, t1/2, AUC0-last, CL).

  Up to 90 days

• Effect of ALN-TTRSC (revusiran) on transthyretin (TTR) (Determination of % Lowering of TTR to pretreatment/Baseline Levels).

  Up to 90 days

• Effect of ALN-TTRSC (revusiran) on vitamin A (Determination of % Lowering of vitamin A to pretreatment/Baseline Levels).

  Up to 90 days

• Effect of ALN-TTRSC (revusiran) on retinol binding protein (RBP) (Determination of % Lowering of RBP to pretreatment/Baseline Levels).

  Up to 90 days

Study Arms (2)

ALN-TTRSC (revusiran)

ACTIVE COMPARATOR

Drug: ALN-TTRSC (revusiran)

Sterile Normal Saline (0.9% NaCl)

PLACEBO COMPARATOR

Drug: Sterile Normal Saline (0.9% NaCl)

Interventions

ALN-TTRSC (revusiran) DRUG

Ascending doses of ALN-TTRSC (revusiran) by subcutaneous (SC) injection

ALN-TTRSC (revusiran)

Sterile Normal Saline (0.9% NaCl) DRUG

Calculated volume to match active comparator

Sterile Normal Saline (0.9% NaCl)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Body mass index (BMI) must be ≥ 16.5 kg/m2 and ≤ 35.0 kg/m2;
• Female subjects must be of non-childbearing potential; e.g., postmenopausal or pre-menopausal with surgical sterilization;
• Male subjects agree to use appropriate contraception;
• Adequate blood counts, liver and renal function;
• Non-smokers for at least 3 months;
• Willing to give written informed consent and are willing to comply with the study requirements;
• Subject was born in Japan and has lived outside of Japan for \<10 years, and subject's biological parents and grandparents are fully Japanese and were born in Japan (cohorts 19 and 20).

You may not qualify if:

• Known human immunodeficiency virus (HIV) positive status or known or suspected systemic bacterial, viral, parasitic, or fungal infection;
• Subjects with a history of multiple drug allergies or intolerance to SC injection;
• History of drug abuse and/or alcohol abuse;
• Receiving an investigational agent within 3 months prior to study drug administration;
• Considered unfit for the study by the Principal Investigator.

Sponsors & Collaborators

• Alnylam Pharmaceuticals: lead

Study Sites (2)

Clinical Site

Leeds, LS2 9LH, United Kingdom

Location

Clinical Site

London, NW10 7EW, United Kingdom

Location

MeSH Terms

Interventions

revusiran

Study Officials

• Jared Gollob, MD

  Alnylam Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2013
• First Posted: March 20, 2013
• Study Start: March 1, 2013
• Primary Completion: April 1, 2015
• Study Completion: May 1, 2015
• Last Updated: February 5, 2016

Record last verified: 2016-02

Locations

GB (2)